The screenplay for The Big Sick (2017) was written by Emily V. Gordon and her husband Kumail Nanjiani, and it was loosely based on the real-life courtship between them before their marriage in 2007. According to Nanjiani, the idea to make a script about them was first inspired by the film's eventual co-producer, Judd Apatow, when the two met while appearing in a 2012 episode of the "You Made It Weird" podcast. Developed over the course of three years, the script was called semi-autobiographical because, in addition to the two lead characters modeled after them, many of the events occurring during Gordon and Nanjiani's relationship were noted as being portrayed to an extent in the film. Though not part of the original script, a real-life incident involving Holly Hunter heckling an unnamed player during a U.S. Open tennis match inspired a similar scene in the film where Nanjiani's character is heckled during one of his stand-up sets.

The film premiered at the Sundance Film Festival where it was very well received, which started a bidding war between Sony, Focus Features, Amazon and Netflix for the distribution rights. The co-creator of the film, Kumail Nanjiani, wanted the film to have theatrical distribution, which eliminated Netflix from the bidding war since they are not a proponent in that distribution model. The film's distribution rights were eventually bought for around $12 million by Amazon, who is a big proponent of the theatrical experience, with all of its films getting at least some kind of theatrical run. The $12 million deal was one of the largest deals in Sundance's history.

Kumail Nanjiani personally contacted Anupam Kher about taking the role of his father, Azmat. Kher accepted the role after learning that Nanjiani's real father personally expressed a desire for him to take the role.

While writing the script, Kumail Nanjiani wanted his on-screen family to reflect the jokey and humorous traits of his real-life family. He bemoaned that so many Muslim characters were so frequently depicted as overly serious, and he aimed to avoid that stereotype.

While searching for funding, the producers submitted the script to a variety of potential studios. Within three hours of submission, FilmNation made an offer to fund the whole movie, no strings attached.

In the film, it is mentioned more than once that Kumail Nanjiani is a fan of the TV series The X-Files (1993). In reality, Kumail Nanjiani actually appeared in an episode of The X-Files (1993) in 2016.

In November 2016, Kumail Nanjiani was a guest on the NPR podcast "Pop Culture Happy Hour." When one of the podcast's hosts, Linda Holmes, invited him to plug his upcoming movie (which at the time was still filming), he said, "My wife and I wrote a movie and I'm in it, and it's going to come out next year. Right now it's called 'The Big Sick,' but the name's going to change. So just look for the rom-com about a brown man and a white woman, starring me."

Kumail Nanjiani was both excited and nervous about writing the script. Five years had passed since his wife Emily V. Gordon's health scare, but the feelings from the experience were still fresh in his mind.

Director Michael Showalter commented on the second act's darker (though still humorous) tone after Emily goes into her coma. He referred to how the movie approaches life, stating, "No matter how bad a situation gets, you've got to have humor."

Composer Michael Andrews initially incorporated Eastern-style music into his score to help illustrate the film's themes of culture clash and assimilation. This idea was eventually scrapped as Andrews said it "felt forced."

Rehearsals for the film were nearly delayed when actor Anupam Kher was unable to travel from Mumbai, India to New York, due to an issue with his visa. Fortunately, the problem was quickly resolved and production commenced as scheduled.

In a nod to the fact that both the character of Kumail and the real-life Kumail Nanjiani are fans of the television series The X-Files (1993), in this movie, Kumail's cellphone ringtone is the "Theme from The X-Files" by Mark Snow.

Spoilers

The trivia items below may give away important plot points.

In this movie, when the character of Kumail finally tells his parents that he is (1) in love with Emily; (2) Emily is not Pakistani; and (3) Emily is very (maybe mortally) ill, Kumail's mother immediately shuns him (telling him "you are not my son") and remains quite angry with him for the duration of the movie, only showing a small sign of thawing at the very end of the movie. During an "All Things Considered" interview with the real Kumail Nanjiani and his real-life wife and co-screenwriter, Emily V. Gordon, Nanjiani said that this scene was one way in which his real life was very different from its depiction in this movie--that in reality, when his mother first heard about Emily and her serious illness, she was very concerned and supportive, and it was only once Emily was out of the coma and it was clear that she would recover that Mrs. Nanjiani expressed her anger at Kumail for dating a white woman and for only pretending to be amenable to an arranged marriage to a Pakistani woman. Gordon added that in their real lives, Kumail's mother "never, never once, never came close to her disowning" Kumail.

The fight between Emily and Kumail, when Emily discovers the pictures of Pakistani women in Kumail's room, never happened in real life. The real Emily, however, did recall how tension had arisen between the two after Kumail wouldn't introduce her to his family.

Co-writer Emily V. Gordon revealed in an interview with Empire magazine that one of the most difficult scenes to write was the one where it's revealed that Terry (Ray Romano) had an affair. This didn't occur in real life, and was suggested by producer Judd Apatow. Gordon found it very hard to discuss this subplot with her real parents.